Pharmacology: Pharmacodynamics: Piperacillin is a broad spectrum, semi synthetic penicillin active against many gram-positive and gram-negative aerobic and anaerobic bacteria. It exerts bactericidal activity by inhibition of both septum and cell wall synthesis.
Tazobactam, a triazolyl-methyl penicillanic acid sulfone, is a potent inhibitor of many β-lactamases, in particular the plasmid mediated enzymes which commonly cause resistance to penicillins and cephalosporins including the 3rd generation cephalosporins.
The presence of Tazobactam in Tapicin enhances and extends the antibiotic spectrum of piperacillin to include many β-lactamases-producing bacteria normally resistant to it and to other β-lactam antibiotics. This combination is highly active against piperacillin-sensitive microorganisms as well as β-lactamase-producing, piperacilline-resistant microorganisms.
Gram-Negative Bacteria: Most plasmid mediated β-lactamase- and non-β-lactamase-producing strains of E.coli and Klebsiella sp., (including K.oxytoca, K. pneumoniae), Proteus sp. (including P. vulgaris, P. mirabilis), Salmonella and Shigella spp., Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella sp. (including M. catarrhalis), Haemophilus sp. (including H. influenzae, H. parainfluenzae), Pasteurella multocida, Yersinia and Campylobacter spp., Gardnerella vaginalis. Many chromosomally-mediated β-lactamase-and non-β-lactamase producing strains of Enterobacter sp. (including E. cloacea, E. aerogenes), Citrobacter sp. (including C. freundii, C. diversus), Providencia sp., Morganella morganii, Serratia sp. (including S. marcescens, S. liquefaciens), Pseudomonas aeruginosa and other Pseudomonas sp. (including P. cepacia, P. fluorescens), Xanthomonas maltophilia, Acinetobacter sp.
Gram-Positive Bacteria: β-lactamase- and non-β-lactamase-producing strains of streptococci (S. pneumoniae, S. pyogenes, S. bovis, S. agalactiae, S. viridans, Groups C and G), enterococci (E. faecalis), Staphylococcus aureus (not methicillin-resistant S. aureus), S. saprophyticus, S. epidermidis (coagulase-negative staphylococci), corynebacteria, Listeria monocytogenes, Nocardia sp.
Anaerobic Bacteria: β-lactamase- and non-β-lactamase-producing anaerobes, eg Bacteroides sp. (including B. bivius, B. disiens, B. capillosus, B. melaninogenicus, B. oralis), the Bacteroides fragilis group (including B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron, B. uniformis, B. asaccharolyticus) as well as, Peptostreptococcus and Fusobacterium spp., Eubacterium group, Clostridia sp. (including C. difficile, C. perfringes), Veillonella and Actinomyces spp.
Pharmacokinetics: Peak plasma concentrations of piperacillin and tazobactam are attained immediately after completion of an IV infusion of this product.
The plasma half-life of piperacillin and of tazobactam ranged from 0.7-1.2 hours and was unaffected by dose or duration of infusion.
Piperacillin is metabolized to a minor microbiologically active desethyl metabolite, while tazobactam to a single metabolite that lacks pharmacological and antibacterial activities.
Both piperacillin and tazobactam are eliminated via the kidney by glomerular filtration and tubular secretion.
Piperacillin is excreted rapidly as unchanged drug with 68% of the administered dose excreted in urine.
Tazobactam and its metabolite are eliminated primarily by renal excretion with 80% of the administered dose excreted as unchanged drug and the remainder as the single metabolite.
Piperacillin, tazobactam and desethyl piperacillin are also excreted into the bile.
Piperacillin and tazobactam are widely distributed into tissues and body fluids including intestinal mucosa, gallbladder, lung, female reproductive tissues (uterus, ovary and fallopian tube), interstitial fluid and bile.
Mean tissue concentrations are generally 50-100% of those in plasma.
Half-life for piperacillin and tazobactam increases with decreasing creatinine clearance in renal impairment (see Dosage & Administration).
Hemodialysis removes 30-40% of piperacillin/tazobactam dose with an additional 5% of the tazobactam dose removed as the tazobactam metabolite.
Peritoneal dialysis removes approximately 6 and 21% of the piperacillin and tazobactam doses, respectively, with up to 16% of the tazobactam dose removed as the tazobactam metabolite.